Linear electrode array to treat mitral regurgitation

ABSTRACT

A method and apparatus are disclosed for treating mitral regurgitation with electrical stimulation. By providing pacing stimulation to a region of the left ventricle in proximity to the mitral valve apparatus in a manner which pre-excites the region during early ventricular systole, a beneficial effect is obtained which can prevent or reduce the extent of mitral regurgitation.

FIELD OF THE INVENTION

This invention pertains to cardiac devices such as pacemakers and othertypes of devices for treating cardiac dysfunction.

BACKGROUND

The tricuspid and mitral valves, also referred to as theatrioventricular valves, separate the atrium and ventricle on the rightand left sides of heart, respectively. The function of theatrioventricular valves is to allow flow of blood between the atrium andventricle during ventricular diastole and atrial systole but prevent thebackflow of blood during ventricular systole. The mitral valve iscomposed of a fibrous ring called the mitral annulus located between theleft atrium and the left ventricle, the anterior and posterior leaflets,the chordae tendineae, and the papillary muscles. The leaflets extendfrom the mitral annulus and are tethered by the chordae tendineae to thepapillary muscles which are attached to the left ventricle. The functionof the papillary muscles is to contract during ventricular systole andlimit the travel of the valve leaflets back toward the left atrium. Ifthe valve leaflets are allowed to bulge backward into the atrium duringventricular systole, called prolapse, leakage of blood through the valvecan result. The structure and operation of the tricuspid valve issimilar.

Mitral regurgitation (MR), also referred to as mitral insufficiency ormitral incompetence, is characterized by an abnormal reversal of bloodflow from the left ventricle to the left atrium during ventricularsystole. This occurs when the leaflets of the mitral valve fail to closeproperly as the left ventricle contracts, thus allowing retrograde flowof blood back into the left atrium. Tricuspid regurgitation (TR) occursin a similar manner. MR and TR can be due to a variety of structuralcauses such as ruptured chordae tendineae, leaflet perforation, orpapillary muscle dysfunction. Functional MR and TR may also occur inheart failure patients due to annular dilatation or myocardialdysfunction, both of which may prevent the valve leaflets from coaptingproperly.

In acute mitral valve regurgitation, the incompetent mitral valve allowspart of the ventricular ejection fraction to reflux into the leftatrium. Because the atrium and ventricle are not able to immediatelydilate, the volume overload of the atrium and ventricle results inelevated left atrial and pulmonary venous pressures and acute pulmonaryedema. The reduction in forward stroke volume due to the reflux throughthe regurgitant valve reduces systemic perfusion, which if extremeenough can lead to cardiogenic shock. In chronic mitral valveregurgitation, on the other hand, the left atrium and ventricle dilateover time in response to the volume overload which acts as acompensatory mechanism for maintaining adequate stroke volume. The leftventricular dilatation, however, may further prevent proper coaptationof the mitral valve leaflets during systolic ejection, leading toprogression of the left ventricular dilatation and further volumeoverload. Patients with compensated MR may thus remain asymptomatic foryears despite the presence of severe volume overload, but most peoplewith MR decompensate over the long term and either die or undergo acorrective surgical procedure. In order to provide early and appropriateintervention, patients with MR may be identified by clinical examinationand/or with specific imaging modalities such as echocardiography.

SUMMARY

A method and apparatus are disclosed for treating mitral or tricuspidregurgitation with electrical stimulation. In one embodiment, pacingstimulation is provided to a region of the ventricle in proximity to themitral or tricuspid valve apparatus in a manner which pre-excites theregion during early ventricular systole in order prevent or reduce theextent of mitral regurgitation. A more uniform stimulation of thepre-excited region may be obtained by the use of a linear electrodearray as disclosed herein.

This summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present invention isdefined by the appended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B illustrate the mechanisms involved in mitralregurgitation.

FIG. 2 illustrates an exemplary implantable device for deliveringpre-excitation pacing to a mitral valve region.

FIG. 3 illustrates an exemplary linear electrode array.

DETAILED DESCRIPTION

The most common method presently available for definitive treatment ofMR is surgical intervention involving repair of the mitral valve orreplacement with a mechanical or transplanted valve. In order to provideearly and appropriate intervention, patients with MR may be identifiedby clinical examination and/or with specific imaging modalities such asechocardiography. The present disclosure deals with a method andapparatus for treating mitral (or tricuspid) regurgitation withelectrical pacing therapy. Pacing therapy applied in this manner may beused to treat MR either in place of or in addition to the conventionalsurgical options.

As mentioned above, one mechanism responsible for the development of MRis dilation of the left ventricle which correspondingly dilates themitral annulus and/or alters its position, thereby preventing propercoaptation of the valve leaflets. Such ventricular dilation occurs inpatients suffering heart failure or subsequent to a myocardialinfarction as a compensatory response to decreased cardiac output. Heartfailure patients may also suffer from electrical conduction deficitswhich alter the normal activation patterns of the myocardium duringsystole. Such electrical conduction deficits may result in abnormaltiming of papillary muscle contraction which also prevents properleaflet coaptation. FIGS. 1A and 1B are schematic diagrams of the leftventricle LV, left atrium LA, posterior mitral leaflet PML, anteriormitral leaflet AML, aorta AO, papillary muscle PM, and chordea tendineaeCT. FIG. 1A illustrates the normal situation during ventricular systolewhere the posterior and anterior leaflets are tethered by the chordeatendineae and papillary muscle to the posterior wall of the leftventricle in such a manner that the valve leaflets are coapted, thuspreventing reflux flow into the atrium. As the ventricle contractsfurther, corresponding contraction of the papillary muscle maintains thecoaptation of the valve leaflets and prevents them from prolapsing intothe atrium. FIG. 1B illustrates the situation where the ventricle isabnormally dilated so as to cause mitral regurgitation. The outwarddisplacement of the ventricular walls and papillary muscle causes anaugmented tethering force to be applied to the valve leaflets whichprevents proper coaptation and allows reflux flow RF into the atrium. Asthe ventricle contracts further, simultaneous contraction of thepapillary muscle maintains the augmented tethering force and preventsvalve closure.

It has been found that pacing therapy may be applied in such a mannerthat mitral regurgitation is either prevented or lessened in degree incertain patients. In this technique, a pacing electrode is disposed soas to excite a ventricular region in proximity to the regurgitant mitralvalve. If the pacing excitation is timed so as to pre-excite theventricular region in early ventricular systole, the action of themitral valve is modified in a manner which lessens or preventsregurgitation. This may come about in several different ways. If theventricular region around the mitral valvular annulus is pre-excited,that ventricular region contracts during the lower afterload pressurewhich exists during early systole. This may cause the ventricularcontraction to constrict the annulus and allow proper coaptation of thevalve leaflets to occur. Similarly, pre-excitation of the ventricularregion between the valve annulus and the attachment of the papillarymuscle to the ventricular wall causes that ventricular region tocontract against a lower afterload and lessens the augmented tetheringforce which prevents proper coaptation of the valve leaflets.Pre-excitation of the papillary muscle can also lessen the augmentedtethering force by causing the muscle to be relaxed in later systole andthereby allow valve closure in the dilated ventricle.

As described above, the timing of the pacing delivered to a ventricularregion in proximity to the mitral valve should be such that the regionis pre-excited during the early phase of ventricular systole. In apatient with intact native atrioventricular conduction, the timing ofthe pre-excitation may be established with reference to a right or leftatrial sense or pace. The atrioventricular delay interval between theatrial sense or pace and the ventricular pre-excitation pace may then beselected to be slightly shorter than the patient's measured intrinsicatrioventricular interval. In one embodiment, because the intrinsicatrioventricular interval varies with heart rate, the intrinsicatrioventricular interval may be measured for a plurality of differentheart rate ranges and the atrioventricular delay interval for deliveringpre-excitation pacing made to vary accordingly. In a patient either withor without intact native atrioventricular conduction and who iscurrently receiving conventional bradycardia and/or resynchronizationventricular pacing therapy, the timing of the pre-excitation pacingdelivered to a ventricular region in proximity to the mitral valve maybe such that the pre-excitation pace occurs before the conventionalventricular pace (or paces), where the latter may be timed with anatrioventricular delay interval selected for optimum hemodynamics. Theatrioventricular delay interval for the combination of pre-excitationpacing to the mitral valve region and conventional or resynchronizationventricular pacing may also be made to vary with heart rate.

Described below is an exemplary device which may be used to deliverpre-excitation pacing to the mitral valve region of the left ventriclein any of the manners just described. The device is configurable to alsodeliver conventional bradycardia or resynchronization pacing in additionto the pre-excitation pacing. It should be appreciated, however, that adevice for delivering pre-excitation pacing to the mitral valve regionmay possess only those features or components necessary for a particularmode of delivery.

1. Exemplary Device Description

Conventional cardiac pacing with implanted pacemakers involvesexcitatory electrical stimulation of the heart by the delivery of pacingpulses to an electrode in electrical contact with the myocardium. As theterm is used herein, a “pacemaker” should be taken to mean any cardiacdevice, such as an implantable cardioverter/defibrillator, with thecapability of delivering pacing stimulation to the heart, includingpre-excitation pacing to the mitral valve region as described herein. Apacemaker is usually implanted subcutaneously on the patient's chest,and is connected to electrodes by leads threaded through the vessels ofthe upper venous system into the heart. An electrode can be incorporatedinto a sensing channel that generates an electrogram signal representingcardiac electrical activity at the electrode site and/or incorporatedinto a pacing channel for delivering pacing pulses to the site.

A block diagram of an implantable multi-site pacemaker having multiplesensing and pacing channels is shown in FIG. 2. The controller of thepacemaker is made up of a microprocessor 10 communicating with a memory12 via a bidirectional data bus, where the memory 12 typically comprisesa ROM (read-only memory) for program storage and a RAM (random-accessmemory) for data storage. The controller could be implemented by othertypes of logic circuitry (e.g., discrete components or programmablelogic arrays) using a state machine type of design, but amicroprocessor-based system is preferable. As used herein, theprogramming of a controller should be taken to refer to either discretelogic circuitry configured to perform particular functions or to thecode executed by a microprocessor. The controller is capable ofoperating the pacemaker in a number of programmed modes where aprogrammed mode defines how pacing pulses are output in response tosensed events and expiration of time intervals. A telemetry transceiver80 is provided for communicating with an external device 300 such as anexternal programmer. An external programmer is a computerized devicewith an associated display and input means that can interrogate thepacemaker and receive stored data as well as directly adjust theoperating parameters of the pacemaker. The telemetry transceiver 80enables the controller to communicate with an external device 300 via awireless telemetry link. The external device 300 may be an externalprogrammer which can be used to program the implantable device as wellas receive data from it or may be a remote monitoring unit. The externaldevice 300 may also be interfaced to a patient management network 91enabling the implantable device to transmit data and alarm messages toclinical personnel over the network as well as be programmed remotely.The network connection between the external device 300 and the patientmanagement network 91 may be implemented by, for example, an internetconnection, over a phone line, or via a cellular wireless link.

The embodiment shown in FIG. 2 has multiple sensing/pacing channels,where a pacing channel is made up of a pulse generator connected to anelectrode while a sensing channel is made up of the sense amplifierconnected to an electrode. A MOS switching network 70 controlled by themicroprocessor is used to switch the electrodes from the input of asense amplifier to the output of a pulse generator. The switchingnetwork 70 also allows the sensing and pacing channels to be configuredby the controller with different combinations of the availableelectrodes. The channels may be configured as either atrial orventricular channels allowing the device to deliver conventionalventricular single-site pacing, biventricular pacing, or multi-sitepacing of a single chamber, where the ventricular pacing is deliveredwith or without atrial tracking. In an example configuration, threerepresentative sensing/pacing channels are shown. A right atrialsensing/pacing channel includes ring electrode 43 a and tip electrode 43b of bipolar lead 43 c, sense amplifier 41, pulse generator 42, and achannel interface 40. A right ventricular sensing/pacing channelincludes ring electrode 23 a and tip electrode 23 b of bipolar lead 23c, sense amplifier 21, pulse generator 22, and a channel interface 20,and a left ventricular sensing/pacing channel includes ring electrode 33a and tip electrode 33 b of bipolar lead 33 c, sense amplifier 31, pulsegenerator 32, and a channel interface 30. The channel interfacescommunicate bi-directionally with a port of microprocessor 10 andinclude analog-to-digital converters for digitizing sensing signalinputs from the sensing amplifiers, registers that can be written to foradjusting the gain and threshold values of the sensing amplifiers, andregisters for controlling the output of pacing pulses and/or changingthe pacing pulse amplitude. In this embodiment, the device is equippedwith bipolar leads that include two electrodes which are used foroutputting a pacing pulse and/or sensing intrinsic activity. Otherembodiments may employ unipolar leads with single electrodes for sensingand pacing. The switching network 70 may configure a channel forunipolar sensing or pacing by referencing an electrode of a unipolar orbipolar lead with the device housing or can 60.

The controller controls the overall operation of the device inaccordance with programmed instructions stored in memory. The controllerinterprets electrogram signals from the sensing channels, implementstimers for specified intervals, and controls the delivery of paces inaccordance with a pacing mode. The sensing circuitry of the pacemakergenerates atrial and ventricular electrogram signals from the voltagessensed by the electrodes of a particular channel. An electrogramindicates the time course and amplitude of cardiac depolarization andrepolarization that occurs during either an intrinsic or paced beat.When an electrogram signal in an atrial or ventricular sensing channelexceeds a specified threshold, the controller detects an atrial orventricular sense, respectively, which pacing algorithms may employ totrigger or inhibit pacing. An impedance sensor 95 is also interfaced tothe controller for measuring transthoracic impedance. The transthoracicimpedance measurement may be used to derive either respiratory minuteventilation for rate-adaptive pacing modes or, as described below,cardiac stroke volume for modulating the delivery of pre-excitationpacing to the mitral or tricuspid valve region.

In order to deliver pre-excitation pacing to the mitral valve region ofa ventricle, one or more pacing channels are configured, each with anelectrode disposed near the region to be pre-excited. Sensing channelsfor the pre-excited region may or may not also be configured. Thepre-excitation ventricular pacing may then be delivered in accordancewith a conventional atrial tracking bradycardia pacing algorithm (e.g.,VDD or DDD) with the atrioventricular delay interval set to a valuewhich results in pre-excitation of the mitral or tricuspid valve regionduring ventricular systole. Such pre-excitation pacing of the mitralvalve region may also be delivered in conjunction with ventricularresynchronization therapy. Ventricular resynchronization therapy is mostcommonly applied in the treatment of patients with heart failure due toleft ventricular dysfunction which is either caused by or contributed toby left ventricular conduction abnormalities. In such patients, the leftventricle or parts of the left ventricle contract later than normalduring systole which thereby impairs pumping efficiency. In order toresynchronize ventricular contractions in such patients, pacing therapyis applied such that the left ventricle or a portion of the leftventricle is pre-excited relative to when it would become depolarized inan intrinsic contraction. Optimal pre-excitation in a given patient maybe obtained with biventricular pacing or with left ventricular-onlypacing.

In one embodiment, the device is programmed to pace the ventricle withthe regurgitant valve at a first programmed AV interval subsequent to anatrial sense or pace and pace the ventricle contralateral to theventricle with the regurgitant valve at a second programmed AV intervalsubsequent to an atrial sense or pace. (It should be appreciated thatspecifying separate AV delay intervals for the two ventricles isequivalent to specifying a biventricular offset interval between rightand left ventricular paces.) A patient's intrinsic AV interval betweenan atrial sense or pace and a sense in the ventricle with theregurgitant valve may be measured, and a programmed AV interval whichoptimally pre-excites the ventricular region in proximity to theregurgitant valve may be computed as a function of the measuredintrinsic AV interval.

2. Electrodes for Pre-excitation of Mitral Valve Region

In order to provide optimal pre-excitation pacing to the mitral valveregion, the electrical stimulation should be applied in a manner whichcauses simultaneous depolarization of a selected region of themyocardium. The electric field from a point source such as aconventional pacing electrode uniformly depolarizes only a relativelysmall myocardial region. In order to provide uniform stimulation to alarger region which encompasses the relevant portions of the mitralapparatus a linear electrode array may be employed as the pre-excitationpacing electrode. Such a linear electrode array may be constructed as anelongated structure with a plurality of electrodes along its length. Theplurality of electrodes in the array may be driven by the same orseparate pacing channels of the implantable device. A linear electrodearray provides more uniform stimulation of a selected myocardial regionand facilitates optimal positioning of the electrodes near the region tobe pre-excited. The array may be positioned via the coronary sinus orarteries for epicardial activation near the dysfunctional mitral valveregion. The linear electrode array may also take the form of aneedle-like structure which may be inserted through the myocardium andpositioned endocardially adjacent the papillary muscle. FIG. 3illustrates part of an exemplary linear electrode array 300 having aplurality of electrodes 301 a through 301 c which is positioned adjacentthe papillary muscle PM. Simultaneous activation of the electrodesprovides uniform excitation to the papillary muscle which, as describedabove, can be beneficial in reducing mitral regurgitation.

3. Control of Pre-excitation Pacing

It may be desirable in certain patients to control the delivery ofpre-excitation pacing to the mitral valve region so that such pacing isdelivered only when it is needed to lessen mitral regurgitation.Accordingly, the device may be programmed to switch between a firstpacing mode which pre-excites the ventricular region in proximity to theregurgitant valve relative to the rest of the ventricle duringventricular systole in order to reduce valve regurgitation and a secondpacing mode in accordance with a measured physiological variable. Thesecond pacing mode may be no pacing at all or any other pacing mode suchas one which provides ventricular resynchronization therapy. Also, oneor more of the programmed AV intervals for the first pacing mode may bemade different from the corresponding AV intervals for the second pacingmode, and one or more pacing sites for the first pacing mode may be madedifferent from the pacing sites of the second pacing mode. As mitralregurgitation produces volume overloading of both the left atrium andventricle, an appropriate physiological variable for the purpose ofswitching between the first and second pacing modes in order to modulatethe frequency or duration of the pre-excitation pacing is cardiac bloodvolume (or stroke volume). Cardiac blood volume or stroke volume may bedetermined from a transthoracic impedance measurement usingappropriately placed electrodes.

The description set forth above has dealt specifically with techniquesand apparatus for treating mitral regurgitation with ventricularpre-excitation pacing. It should be appreciated that same techniques andapparatus could be used to treat either tricuspid or mitralregurgitation by pre-exciting the regurgitant valve region in eitherventricle. If both atrio-ventricular valves are regurgitant,pre-excitation pacing may be applied to the atrio-ventricular valveregion of both ventricles.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Other such alternatives, variations, and modifications are intended tofall within the scope of the following appended claims.

1. A method comprising: identifying a regurgitant mitral or tricuspidvalve in a patient; implanting a cardiac rhythm management device in thepatient for delivering pacing therapy to the heart through one or morepacing electrodes; disposing a linear electrode array structure having aplurality of pacing electrodes arranged therein so as to excite aventricular region in proximity to the regurgitant valve in the sameventricle as the regurgitant valve; measuring an intrinsic AV intervalbetween an atrial sense or pace and a sense in the ventricle with theregurgitant valve; computing a first programmed AV interval whichoptimally pre-excites the ventricular region in proximity to theregurgitant valve as a function of the measured intrinsic AV interval,wherein the first programmed AV interval is made to be shorter than themeasured intrinsic AV interval and is made to vary with heart rate; and,delivering pacing therapy to the ventricular region in proximity to theregurgitant valve upon expiration of the first programmed AV intervalfollowing an atrial sense or pace to thereby pre-excite the ventricularregion in proximity to the regurgitant valve relative to the rest of theventricle during ventricular systole.
 2. The method of claim 1 furthercomprising pacing the ventricle contralateral to the ventricle with theregurgitant valve at a second programmed AV interval subsequent to anatrial sense or pace.
 3. The method of claim 2 further comprisingswitching between a first pacing mode which pre-excites the ventricularregion in proximity to the regurgitant valve relative to the rest of theventricle during ventricular systole in order to reduce valveregurgitation and a second pacing mode which provides ventricularresynchronization therapy in accordance with a measured physiologicalvariable.
 4. The method of claim 3 wherein one or more of the programmedAV intervals for the first pacing mode are different from thecorresponding AV intervals for the second pacing mode.
 5. The method ofclaim 4 wherein one or more pacing sites for the first pacing mode aredifferent from the pacing sites of the second pacing mode.
 6. The methodof claim 3 wherein the measured physiological variable is cardiac bloodvolume determined from a transthoracic impedance measurement.
 7. Themethod of claim 1 further comprising controlling the delivery ofpre-excitation pacing to the ventricular region in proximity to theregurgitant valve in accordance with a measurement of cardiac bloodvolume.
 8. The method of claim 1 wherein the regurgitant valve is themitral valve and further comprising disposing the linear electrode arraystructure so as to pre-excite a papillary muscle during ventricularsystole.
 9. The method of claim 8 further comprising disposing thelinear electrode array structure endocardially near a papillary muscle.10. The method of claim 1 wherein the linear electrode array structureis epicardially disposed near the ventricular region in proximity to theregurgitant valve.